Fig. 2

Ultrastructural changes in the organ of Corti. Representative light (A, B, E, F, K, L) and transmission electron (C, D, G–J, M, N) micrographs show the organ of Corti from p43^−/− (A–J) and WT mice (K–N). A–D 1-month-old p43^−/− mice. The organ of Corti shows adult-like structural characteristics with well-opened tunnel of Corti (tC) and spaces of Nuel (Ns) and normally shaped tectorial (tm) and basilar (bm) membranes (A). The 3 OHCs (O) above the Deiters cells (D), and the IHC (I) are present (A). Densely packed myelinated nerve fibers (nf) and schwann cells (s) are visible in the spiral lamina (B). The nucleus (n) of IHC is well positioned in the upper half of the cell body (C). The stereocilia (arrow) are erect. Beneath the basal pole of the IHC, the inner spiral bundle (isb) contains numerous nerve fibers. The inset in C shows a typical synaptic contact between the IHC and the extremity of a radial afferent fiber (a). Note the synaptic ribbon (arrowhead) within the IHC. ip, inner pillar cell. Note the apparently normal OHC with erect stereocilia (arrow) and basally located nucleus (D). Most of its mitochondria are damaged (white arrowheads and upper inset in D). Lower inset in D: a typical efferent synapse at the basal pole of a neighboring OHC (e: efferent ending). E–J 12 months of age p43^−/− mice. Shown is an organ of Corti containing IHC, but lacking OHC (E). In the area of the missing OHCs (delineated by the black square), an epithelial scar is formed by Deiters (D) and Hensen (H) cells (E). In the osseous spiral lamina, empty spaces (asterisks) are visible in the bundle of nerve fibers (F). The IHC is deformed and contains damaged mitochondria (white arrowheads), an exuberant network of endoplasmic reticulum (black arrowheads) contacting the mitochondria, and large aggregates of membranous material resembling reticulum debris (within the black square, G). The inner spiral sulcus contains only few afferent (a) nerve fibers (G). H–J Enlargement of organelles seen in the IHC shown in G. H Two closely linked mitochondria with the absence of their cristae, and a portion of the lower mitochondrion is free of matrix. Note well-defined endoplasmic reticulum (arrowhead) in contact with the two mitochondria. I Accumulation of membranous material such as endoplasmic reticulum debris. J Immature-like afferent synapse at the basal pole of the IHC. Note the multiple synaptic ribbons (arrowheads) in the IHC and the elongated postsynaptic density in the afferent fiber. K–N: 12 months of age WT mice. K The organ of Corti contains the IHC and the OHCs, but the OHC from the first row is damaged (arrow). L Among the nerve fibers, some empty spaces (asterisk) are visible in the spiral lamina. M The IHC has a typical shape and erect stereocilia (arrow). Note the large autophagic vacuoles (v) within the cytoplasm of the cell and the swollen afferent dendrite extremities (asterisks) at its basal pole. N OHC from the first row, showing a distorted cell body (asterisk), bent and fused stereocilia (arrow) and some damaged mitochondria (arrowheads). Note the cell debris (in the black square) floating within the spaces of Nuel. A, E, K = 50 μm. C, G, M = 10 μm. B, D, F, L, N = 5 μm. H, J = 1 μm. I = 0,5 μmm. Inset C and lower inset D = 1 μm. Upper inset D = 0.5 μm. N = 4 cochleae per age and strain